The object of our study is to provide a coherent basis for the understanding of the electromagnetic properties and biochemical reactivity of cytochrome P450. The oxidative reactive cycle of P450s is well characterized and involves four stable states of the enzyme and a fifth, reactive state which carries out the oxidation. Each of the stable states has a number of characteristic electromagnetic properties which can be directly related to the immediate environment around the heme unit as the protein proceeds through the reaction cycle. Using the method of quantum chemistry, we propose to characterize the conformation, electronic structure and spin distribution of each of the stable staes of the heme unit. The results will be used to calculate electromagnetic properties which can then be compared to experiment. In addition to quadrupole splitting, hyperfine interactions, and g values observed in Mossbauer and electron spin resonance spectra, improved methodology now allows us to calculate and assign electronic absorbtion spectra. Such calculations provide a link between molecular features and observed properties, allowing a realistic model for each of the 4 stages to be obtained which is consistent with experimental behavior and which furnishes a more detailed description of the active site than can be obtained from the experiments alone. We also plan to explore plausible models for the active state itself and to model reaction pathways involving the transfer of an electrophilic oxygen atom to different classes of substrates. Such studies should help elucidate the mechanism of P450-mitigated hydroxylations and epoxidations, for example, resolving such long-standing questions as to whether they involve radical mechanisms and proceed by insertions or alternative pathways. Finally, we plan to begin studies of the anaerobic reductive metabolism in which P450s have recently been implicated.